Nahrevanian Hossein, Dascombe Michael J
School of Biological Sciences, The University of Manchester, UK.
Parasite Immunol. 2002 Sep-Oct;24(9-10):471-8. doi: 10.1046/j.1365-3024.2002.00490.x.
Nitric oxide (NO) is a putative mediator of the immunological and/or pathological responses to malaria, consequently it is a potential target for novel drug therapy. Numerous cell types increase expression of inducible nitric oxide synthase (iNOS) under inflammatory conditions, the most relevant stimuli being cytokines and endotoxins. In this study the expression of iNOS mRNA in several target organs (brain, liver, spleen) of malaria have been investigated in MF1 mice during lethal Plasmodium (P.) berghei and non-lethal P. c. chabaudi infection. In P. berghei malaria, iNOS mRNA decreased in liver and was unchanged in spleen during the period of rising parasitaemia, but increased in both organs late in the infection, when parasitaemia was high and death imminent. In mice infected with P. c. chabaudi, spleen iNOS mRNA increased progressively throughout the early, peak and recovery periods of parasitaemia, but decreased in liver. Brain iNOS mRNA decreased in samples collected throughout the time courses of both infections. Hence it is evident that changes in iNOS mRNA in murine malaria depend upon the tissue, day of infection, degree of parasitaemia and strain of Plasmodium. These data indicate induction of iNOS mRNA in the spleen has a role in combating these strains of Plasmodium in MF1 mice. Failure to clear lethal P. berghei parasitaemia was associated with increased iNOS mRNA expression in the liver, which may contribute to the pathology of this malaria.
一氧化氮（NO）被认为是疟疾免疫和/或病理反应的介质，因此它是新型药物治疗的潜在靶点。在炎症条件下，许多细胞类型会增加诱导型一氧化氮合酶（iNOS）的表达，最相关的刺激因素是细胞因子和内毒素。在本研究中，研究了致死性伯氏疟原虫和非致死性约氏疟原虫感染期间，MF1小鼠疟疾的几个靶器官（脑、肝、脾）中iNOS mRNA的表达。在伯氏疟原虫疟疾中，在寄生虫血症上升期间，肝脏中的iNOS mRNA减少，脾脏中的iNOS mRNA无变化，但在感染后期，当寄生虫血症很高且即将死亡时，两个器官中的iNOS mRNA均增加。在感染约氏疟原虫的小鼠中，脾脏iNOS mRNA在寄生虫血症的早期、高峰期和恢复期逐渐增加，但在肝脏中减少。在两种感染的整个病程中采集的样本中，脑iNOS mRNA均减少。因此，很明显，小鼠疟疾中iNOS mRNA的变化取决于组织、感染天数、寄生虫血症程度和疟原虫菌株。这些数据表明，脾脏中iNOS mRNA的诱导在MF1小鼠对抗这些疟原虫菌株中起作用。未能清除致死性伯氏疟原虫的寄生虫血症与肝脏中iNOS mRNA表达增加有关，这可能导致这种疟疾的病理变化。
